Biased N-Glycosylation Site Distribution and Acquisition across the Antibody V Region during B Cell Maturation
| Autor: | Jana Koers, Theo Rispens, Pleuni Ooijevaar-de Heer, Benjamin Nota, Gestur Vidarsson, Ninotska I. L. Derksen, Fleur S. van de Bovenkamp |
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| Přispěvatelé: | Graduate School, AII - Inflammatory diseases, Landsteiner Laboratory |
| Rok vydání: | 2019 |
| Předmět: |
Glycosylation
biology Immunology Immunoglobulin E Molecular biology Isotype carbohydrates (lipids) Affinity maturation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine.anatomical_structure chemistry biology.protein medicine Immunology and Allergy Antibody N-Glycosylation Site Memory B cell B cell 030215 immunology |
| Zdroj: | Journal of immunology (Baltimore, Md., 202(8), 2220-2228. American Association of Immunologists |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.1801622 |
| Popis: | Abs can acquire N-linked glycans in their V regions during Ag-specific B cell responses. Among others, these N-linked glycans can affect Ag binding and Ab stability. Elevated N-linked glycosylation has furthermore been associated with several B cell–associated pathologies. Basic knowledge about patterns of V region glycosylation at different stages of B cell development is scarce. The aim of the current study is to establish patterns of N-glycosylation sites in Ab V regions of naive and memory B cell subsets. We analyzed the distribution and acquisition of N-glycosylation sites within Ab V regions of peripheral blood and bone marrow B cells of 12 healthy individuals, eight myasthenia gravis patients, and six systemic lupus erythematosus patients, obtained by next-generation sequencing. N-glycosylation sites are clustered around CDRs and the DE loop for both H and L chains, with similar frequencies for healthy donors and patients. No evidence was found for an overall selection bias against acquiring an N-glycosylation site, except for the CDR3 of the H chain. Interestingly, both IgE and IgG4 subsets have a 2-fold higher propensity to acquire Fab glycans compared with IgG1 or IgA. When expressed as rmAb, 35 out of 38 (92%) nongermline N-glycosylation sites became occupied. These results point toward a differential selection pressure of N-glycosylation site acquisition during affinity maturation of B cells, which depends on the location within the V region and is isotype and subclass dependent. Elevated Fab glycosylation represents an additional hallmark of TH2-like IgG4/IgE responses. |
| Databáze: | OpenAIRE |
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